Studies on an apolipoprotein C-II variant occurring in Caucasians

Apolipoproteins C (apo C-II, apo C-III0, apo C-III1 and apo C-III2) from delipidated very low density lipoproteins (VLDL) of 522 normo- and hyperlipoproteinemic Caucasians were screened by analytical isoelectric focusing. The immobilized pH gradient used was pH 4.0-5.0 with 7 M urea, which raised the apparent pH range to 4.8-5.7. As identified by immunoblotting, six unrelated persons had two major isoforms of apo C-II, the normal apo C-II-1 (which focuses between apo C-III0 and apo C-III1) and a variant, designated apo C-II-v according to Huff et al., focusing between apo C-III1 and apo C-III2 due to a more acidic pI. In narrow pH gradients, apo C-II-v can readily be discriminated from the minor isoform, apo C-II-2, due to its slightly more basic pI, corresponding to a difference of 0.01 pH units. Neuraminidase treatment did not alter the pI of apo C-II-v and on two-dimensional electrophoresis the molecular weights of apo C-II-1 and apo C-II-v were indistinguishable. The frequency of apo C-II-v was 1.2%. It was the same in males and females and was independent of hypertriglyceridemia. The autosomal codominant inheritance could be demonstrated in the pedigree of one family. Electroblotting of apo C-II-1 and apo C-II-v onto activated glass fiber sheets, followed by amino acid sequence analysis of the amino terminal ends, revealed an exchange of the amino acid lysine at position 19 by threonine in apo C-II-v.(ABSTRACT TRUNCATED AT 250 WORDS)